Mutation analysis of related genes in hamartoma polyp tissue of Peutz-Jeghers syndrome

作     者：Zhi Zhang Fu-Xiao Duan Guo-Li Gu Peng-Fei Yu 

作者机构：Air Force Clinical College(Air Force Medical Center)of Anhui Medical UniversityBeijing 100142China Department of General Surgerythe General Hospital of Northern Theater Command PLAShenyang 110016Liaoning ProvinceChina Department of General SurgeryAir Force Medical CenterPLABeijing 100142China 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2020年第26卷第16期

页      面：1926-1937页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：Supported by Major Projects of the Chinese PLA"Thirteenth Five-Year Plan"Logistics Research Subject,No.AKJ15J003 No.AKJ15J001 Incubation Project of Military Medical Science and Technology Youth Cultivation Program,No.17QNP023 Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122. 

主　　题：Peutz-Jeghers syndrome STK11 gene LKB1 gene Sequencing Genetic analysis 

摘      要：BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare disease with clinical manifestations of pigmented spots on the lips,mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors.The clinical heterogeneity of PJS is obvious,and the relationship between clinical phenotype and genotype is still unclear.AIM To investigate the mutation status of hereditary colorectal tumor-associated genes in hamartoma polyp tissue of PJS patients and discuss its relationship with the clinicopathological data of PJS.METHODS Twenty patients with PJS were randomly selected for this study and were treated in the Air Force Medical Center(former Air Force General Hospital)PLA between 2008 and 2017.Their hamartoma polyp tissues were used for APC,AXIN2,BMPR1A,EPCAM,MLH1,MLH3,MSH2,MSH6,MUTYH,PMS1,PMS2,PTEN,SMAD4,and LKB1/STK11 gene sequencing using next-generation sequencing technology.The correlations between the sequencing results and clinical pathological data of PJS were analyzed.RESULTS Fourteen types of LKB1/STK11 mutations were detected in 16 cases(80.0%),of which 8 new mutations were found(3 types of frameshift deletion mutations:c.243delG,c.363_364delGA,and c.722delC;2 types of frameshift insertions:c.144_145insGCAAG,and c.454_455insC;3 types of splice site mutations:c.464+1GT,c.464+1GA,and c.598-1GA);9 cases(45.0%)were found to have 18 types of heterozygous mutations in the remaining 13 genes except LKB1/STK11.Of these,MSH2:c.792+1GA,MSH6:c.3689CG,c.4001+13CCTTAC,PMS1:c.46Ct,and c.922GA were new mutations.CONCLUSION The genetic mutations in hamartoma polyp tissue of PJS are complex and diverse.Moreover,other gene mutations in PJS hamartoma polyp tissue were observed,with the exception of LKB1/STK11 gene,especially the DNA mismatch repair gene(MMR).Colorectal hamartoma polyps with LKB1/STK11 mutations were larger in diameter than those with other gene mutations.